System and method for metabolyte neuronal network analysis

• US 20040106169A1
• Filed: 02/20/2003
• Published: 06/03/2004
• Est. Priority Date: 12/02/2002
• Status: Abandoned Application

• Current Assignee: Daron G. Evans
• Original Assignee: Daron G. Evans
• Inventors: Evans, Daron G.
• Application Number:
  US10/371,008
• Publication Number:
  US 20040106169A1
• Time in Patent Office: Days
• US Class Current: 435/40.5
• CPC Class Codes: G01N 33/4836 using multielectrode arrays

Abstract

The present invention provides a system and method for testing the neuronal effects of a compound and its metabolites. The system (100) includes a microelectrode array (102), a data capture unit (108) communicably coupled to the microelectrode array (104), a processor (110) communicably coupled to the data capture unit (108) and one or more input/output devices (112) communicably coupled to the processor (110). The microelectrode array (102) is capable of supporting genetically modified neuronal cells (104) and measuring neuronal activity. The testing medium containing the compound and the metabolites is extracted from hepatocyte cells (106). The method (400) determines the effects of the metabolites of a sample compound on neuronal cells by exposing a sample compound to hepatocyte cells (406), extracting medium from the exposed cells (408) and exposing the extracted medium to neuronal cells on a microelectrode array (410). The effects of a sample compound and its metabolites versus the effects of a sample compound alone can be determined from a comparison of the data (406).

Claims

1. A method for determining the effects of a compound and on a neuronal cell comprising the steps of:

obtaining a first and a second hepatocyte supernatant, wherein the first hepatocyte supernatant comprises a supernatant from a hepatocyte exposed to a compound;

exposing a first and second neuronal cell on a first and a second microelectrode, respectively to the first and second hepatocyte supernatants, respectively; and

detecting the effects of the first and second hepatocyte supernatants on the first and second neuronal cells with the microelectrodes, wherein a comparison of the measurements from the first and the second microelectrodes are used to determine the effects of the hepatocyte supernatants on neuronal cells.

2. The method of claim 1, wherein the neuronal cell comprises an embryonic stem cell from a knock-out, knock-in, over-expressing transgenic, under-expressing-transgenic, a conditional knockout, a mutant and the like.

3. The method of claim 1, wherein the neuronal cell is from an animal knock-out, knock-in, over-expressing transgenic, under-expressing-transgenic, a conditional knockout, a mutant and the like.

4. The method of claim 1, wherein the neuronal cells are selected from the frontal cortex, the auditory cortex, the visual cortex, the hippocampus or the spinal cord.

5. The method of claim 1, wherein the heptatocyte cells are selected from an wild-type animal, a genetically modified animal or an immortalized cell line.

6. The method of claim 1, wherein the hepatocyte cell is from an animal knock-out, knock-in, over-expressing transgenic, under-expressing-transgenic, a conditional knockout, a mutant and the like.

7. The method of claim 1, wherein the neuronal cells or the hepatocyte cells include one or more types of neuronal or hepatic cells, respectively.

8. The method of claim 1, wherein the neuronal cells or hepatocyte cells form a portion of a neural tissue or hepatic tissue, respectively.

9. The method of claim 1, wherein the hepatocyte supernatant comprises both the compound and hepatic metabolites of the compound.

10. The method of claim 1, wherein the hepatocyte supernatant comprises hepatic metabolites of the compound.

11. A method for determining the effects of a compound and the metabolites of the compound on a neuronal cell comprising the steps of:

growing a first and second hepatocyte cell culture a compound, wherein the first hepatocyte cell culture is exposed to a compound;

obtaining the medium from the first and second hepatocyte cell cultures;

applying the medium from the first and second hepatocyte cell cultures, respectively, to a first and a second neuronal cell grown on first and second microelectrodes;

measuring the activity of the first neuronal cell with the first microelectrode and the second neuronal cell with the second microelectrode; and

comparing the measurements from the first and the second microelectrodes to determine the effects of the medium on the neuronal cells.

12. The method of claim 11, wherein the medium comprises the compound and the compound'"'"'s metabolites.

13. The method of claim 11, wherein the medium comprises the compound'"'"'s metabolites.

14. The method of claim 11, further comprising the step of extracting a supernatant from the medium.

15. The method of claim 11, wherein the medium is cell-free.

16. The method of claim 11, wherein the neuronal cell comprises an embryonic stem cell from a knock-out, knock-in, over-expressing transgenic, under-expressing-transgenic, a conditional knockout, a mutant and the like.

17. The method of claim 11, wherein the neuronal cell is from an animal knock-out, knock-in, over-expressing transgenic, under-expressing-transgenic, a conditional knockout, a mutant and the like.

18. The method of claim 11, wherein the neuronal cells are selected from the frontal cortex, the auditory cortex, the visual cortex, the hippocampus or the spinal cord.

19. The method of claim 11, wherein the heptatocyte cells are selected from from an wild-type animal, a genetically modified animal or an immortalized cell line.

20. The method of claim 11, wherein the hepatocyte cell is from an animal knock-out, knock-in, over-expressing transgenic, under-expressing-transgenic, a conditional knockout, a mutant and the like.

21. The method of claim 11, wherein the neuronal cells or the hepatocyte cells include one or more types of neuronal or hepatic cells, respectively.

22. The method of claim 11, wherein the neuronal cells or hepatocyte cells form a portion of a neural tissue or hepatic tissue, respectively.